Gaa. Ferns et al., PROBUCOL INHIBITS MONONUCLEAR CELL-ADHESION TO VASCULAR ENDOTHELIUM IN THE CHOLESTEROL-FED RABBIT, Atherosclerosis, 100(2), 1993, pp. 171-181
Mononuclear cells, isolated from the blood of hyperlipidaemic patients
, are hyper-reactive and possess an increased propensity to adhere to
vascular endothelial cells. Hyperlipidaemia is also associated with a
dysfunctional endothelium, to which mononuclear cells stick with great
er avidity. In order to assess the importance of lipid peroxidation an
d free-radical generation in these processes, we have investigated the
effects of probucol on mononuclear cell adhesion to vascular endothel
ial cells in vivo and in vitro in the cholesterol-fed rabbit. New Zeal
and White rabbits were fed either: (i) control chow (n = 15), (ii) 2%
cholesterol (n = 11), or (iii) 2% cholesterol with 1 % probucol (n = 1
1). Mononuclear cell adherence to endothelium in the common carotid ar
tery was assessed 5 weeks after the start of the experimental diet usi
ng the Hoechst 33342 staining technique. The 2% cholesterol diet cause
d a more than 6-fold increase in mean mononuclear cell adherence (P <
0.001). Concurrent probucol therapy abrogated the effects of cholester
ol feeding, and in animals in this group, in vivo mononuclear cell adh
erence did not differ significantly from control animals. In vivo mono
nuclear cell adherence was directly related to serum cholesterol level
s (r = 0.68, P < 0.0001) and inversely related to serum probucol conce
ntrations (r = -0.63, P < 0.002). Concurrent probucol therapy also red
uced the in vitro binding of mononuclear cells, isolated from hypercho
lesterolaemic animals, to endothelial cell monolayers (P < 0.01). Thes
e data suggest that the increased binding of mononuclear cells to vasc
ular endothelium of cholesterol-fed rabbits may be a free radical medi
ated process that is inhibited by antioxidants.